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Mikawy NN, Magdy N, Mohamed MH, El-Kosasy AM. Validated HPLC method for simultaneous determination of azelastine hydrochloride fluticasone propionate and oxymetazoline in nasal mucosa and nasopharyngeal swabs from real human samples. Sci Rep 2025; 15:4252. [PMID: 39905047 PMCID: PMC11794526 DOI: 10.1038/s41598-024-82387-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2024] [Accepted: 12/04/2024] [Indexed: 02/06/2025] Open
Abstract
A combination of three co-administrated drugs, such as azelastine hydrochloride (AZT), fluticasone propionate (FP), and oxymetazoline (OXY), is more effective than single therapy for the treatment of seasonal allergy and COVID-19. We established an efficient methodology for the determination of those analytes in spiked nasal mucosa and nasopharyngeal swabs from real human samples. A simple and quick protein precipitation method was used for sample extraction, using acetonitrile. RP-HPLC/DAD method was performed using an Exsil 100 ODS C18 (250 × 4.6 mm, 5 μm) column with an acetonitrile: water (70:30 v/v) solvent system at a flow rate of 0.7 mL/min. A photodiode array detector was applied at 240 nm. A good separation of the three proposed analytes with a short run time of 10 min was noted. Our method was validated according to FDA guidelines for bioanalytical validation methods. Calibration curves were linear in nasal mucosa samples at concentration ranges of 8-125, 10-100, and 10-125 µg/mL, with average recoveries ± SD of 101.56%±0.39, 102.45%±0.86, and 104.61%±4.52 for AZT, FP, and OXY; respectively. The results of precision and accuracy are within acceptable limits. According to stability assays, the three analytes under investigation were stable throughout sample preparation, storage, and injection. Our method was applied to real nasopharyngeal swabs. It shows that the results of the swabs were not affected by gender or age. Good recoveries with low % RSD were observed: 99.03% ± 0.75, 100.02% ± 0.94, and 100.94% ± 1.98 for both genders, and 100.45% ± 0.96, 100.69% ± 1.08, and 100.32% ± 1.53 for different ages for AZT, FP, and OXY; respectively. Moreover, the amount of those drugs in the nasal mucosa was observed for seven hours, and a constant concentration with a low% RSD was noted for the first four hours. Therefore, this method can be applied to monitor the therapeutic dose in the nasal mucosa for the determination of those analytes.
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Affiliation(s)
- Neven N Mikawy
- Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Ain Shams University, Abbassia, Cairo, 11566, Egypt
| | - Nancy Magdy
- Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Ain Shams University, Abbassia, Cairo, 11566, Egypt
| | - Marwa H Mohamed
- Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Ain Shams University, Abbassia, Cairo, 11566, Egypt.
| | - Amira M El-Kosasy
- Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Ain Shams University, Abbassia, Cairo, 11566, Egypt
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Mehraeen E, Yarmohammadi S, Mirzapour P, Zadeh SST, Dehghani S, Molaeipour L, Molla A, Karimi E, Abbaspour F, SeyedAlinaghi S. Treatments for Olfactory Dysfunction in COVID-19: A Systematic Review. Int Arch Otorhinolaryngol 2024; 28:e728-e743. [PMID: 39464360 PMCID: PMC11511580 DOI: 10.1055/s-0044-1786046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2023] [Accepted: 03/06/2024] [Indexed: 10/29/2024] Open
Abstract
Introduction Olfactory dysfunction (OD) has emerged as a notable symptom among coronavirus disease 2019 (COVID-19) patients, with its prevalence varying among different populations. Recognizing the need to provide therapeutic solutions for these individuals, the present study seeks to comprehensively review the current evidence on potential underlying mechanisms and treatment modalities to manage OD in COVID-19 patients. Objective To review the recent evidence on treatments for OD in COVID-19. From the beginning of the study until August 2nd, 2023, we conducted a systematic search on four electronic databases, PubMed, Scopus, Embase, and Web of Science, to find relevant publications. Data Synthesis In the present study, 37 articles were selected for data extraction and included in the final review. The total number of patients was of 3,560 (2,098 female and 1,462 male subjects). The predominant disorders reported were hyposmia, anosmia, and parosmia. In most of the studies, the pre and postintervention assessments were the same, except for one study, in which the pre-intervention assessment of the disorder was through the SST, Sniffin' Sticks Test (SST), and the post-intervention assessment was through the Visual Analog Scale (VAS) and the 22-item Sinonasal Outcome Test (SNOT-22). The findings suggest olfactory training (OT), ivermectin, palmitoylethanolamide, luteolin, and systemic corticosteroids, in combination with topical corticosteroids, are potential therapies for COVID-19 patients with olfactory impairment. Conclusion Although the review suggested several medications for OD treatment, further research must delve into the specific impact of OT, a non-pharmacological modality, regarding the mitigation of OD. By continuing to investigate and refine these therapeutic approaches, we can better support COVID-19 patients and improve their quality of life while navigating the challenges posed by OD.
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Affiliation(s)
- Esmaeil Mehraeen
- Department of Health Information Technology, Khalkhal University of Medical Sciences, Khalkhal, Iran
| | | | - Pegah Mirzapour
- Iranian Research Center for HIV/AIDS, Iranian Institute for Reduction of High-Risk Behaviors, Tehran University of Medical Sciences, Tehran, Iran
| | - Seyed Saeed Tamehri Zadeh
- Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Soheil Dehghani
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Leila Molaeipour
- Department of Epidemiology, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
| | - Ayoob Molla
- School of Medicine, Bushehr University of Medical Sciences, Bushehr, Iran
| | - Elaheh Karimi
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Faeze Abbaspour
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - SeyedAhmad SeyedAlinaghi
- Iranian Research Center for HIV/AIDS, Iranian Institute for Reduction of High-Risk Behaviors, Tehran University of Medical Sciences, Tehran, Iran
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Coggins JM, Saito MH, Cook R, Urata S, Urata M, Harsell NL, Tan WN, Figueira BT, Bradley M, Quadri NZ, Saripada JAI, Reyna RA, Maruyama J, Paessler S, Makishima T. Histopathology of the Tongue in a Hamster Model of COVID-19. RESEARCH SQUARE 2024:rs.3.rs-4590482. [PMID: 39011098 PMCID: PMC11247945 DOI: 10.21203/rs.3.rs-4590482/v1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/17/2024]
Abstract
Objective With altered sense of taste being a common symptom of coronavirus disease 2019 (COVID-19), our objective was to investigate the presence and distribution of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) within the tongue over the course of infection. Methods Golden Syrian hamsters were inoculated intranasally with SARS-CoV-2 and tongues were collected at 2, 3, 5, 8, 17, 21, 35, and 42 days post-infection (dpi) for analysis. In order to test for gross changes in the tongue, the papillae of the tongue were counted. Paraffin-embedded thin sections of the tongues were labeled for the presence of SARS-CoV-2 antigen. Results There was no difference in fungiform or filiform papillae density throughout the course of infection. SARS-CoV-2 antigen was observed in the circumvallate papillae taste buds (3-35 dpi) and autonomic ganglia (5-35 dpi), as well as in the serous and mucous salivary glands of the posterior tongue (2-42 dpi). Conclusion The presence and distribution of SARS-CoV-2 suggest that the virus could cause taste disturbance by infecting the circumvallate taste buds. This effect could be exacerbated by a diminished secretion of saliva caused by infection of the serous salivary glands and the autonomic ganglia which innervate them.
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Reda A, Saleh H, Bahgat EA, Fawzy MG. Different Eco-Friendly Spectrophotometric Approaches Including Direct and Manipulations of Zero and Ratio Spectra for Simultaneous Determination of Novel Nasal Spray Combination Used in Seasonal Allergic Rhinitis. J AOAC Int 2024; 107:512-518. [PMID: 38410058 DOI: 10.1093/jaoacint/qsae016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2023] [Revised: 02/02/2024] [Accepted: 02/12/2024] [Indexed: 02/28/2024]
Abstract
BACKGROUND The presentation of rhinitis has drawn increasing attention in recent years due to the possibility of overlap or confusion between allergic rhinitis symptoms and those of COVID-19. Azelastine hydrochloride (AZH) and mometasone furoate (MOF) are two of the most efficient combinations for enhancing the symptoms of seasonal allergic rhinitis. OBJECTIVE This work concerns applying and validating different accurate and simple spectrophotometric approaches for simultaneous quantification of the binary mixture of AZH and MOF in raw material, laboratory-prepared mixtures, and pharmaceutical preparation. Moreover, assessment of the environmental impact of the applied approaches on the environment was also a key goal of this study. METHODS AZH was determined using the direct spectrophotometric (D0) method, while four reliable spectrophotometric approaches namely, induced dual wavelength (IDW), ratio subtraction (RS), ratio difference (RD), and ratio derivative (1DD) were used for MOF determination. RESULTS The methods were validated in line with the International Conference of Harmonization standards. In the AZH range of (5-56 µg/mL) and MOF range of (2-20 µg/mL), the linearity of the proposed approaches was investigated with high accuracy findings. There were no significant differences between the obtained results and those of the reported method when compared statistically. Furthermore, the applied spectrophotometric methods were deemed to be eco-friendly according to Green Analytical Procedure Index (GAPI) and Analytical Greenness Calculator (AGREE) assessment metrics. CONCLUSIONS The applied spectrophotometric methods are simpler, more eco-friendly, and take a shorter time to precisely estimate many measurements compared to the only reported chromatographic analysis. HIGHLIGHTS Neither publications of novel spectrophotometric methods nor reported green ones have been available for simultaneous determination of the binary mixture of AZH and MOF, so this work has a great significance and novelty in the area of pharmaceutical analysis.
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Affiliation(s)
- Alaa Reda
- Egyptian Russian University, Faculty of Pharmacy, Pharmaceutical Chemistry Department, Badr City, Cairo 11829, Egypt
| | - Hanaa Saleh
- Zagazig University, Faculty of Pharmacy, Pharmaceutical Analytical Chemistry Department, Zagazig 44519, Egypt
| | - Eman A Bahgat
- Zagazig University, Faculty of Pharmacy, Pharmaceutical Analytical Chemistry Department, Zagazig 44519, Egypt
| | - Michael Gamal Fawzy
- Egyptian Russian University, Faculty of Pharmacy, Pharmaceutical Chemistry Department, Badr City, Cairo 11829, Egypt
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Parreira LFS, Pinheiro SL, Fontana CE. Photobiomodulation in the Treatment of Dysgeusia in Patients with Long COVID: A Single-Blind, Randomized Controlled Trial. Photobiomodul Photomed Laser Surg 2024; 42:215-224. [PMID: 38416635 DOI: 10.1089/photob.2023.0148] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/01/2024] Open
Abstract
Objective: The aim of this study is to evaluate local and systemic photobiomodulation (PBM) in patients with COVID-19-related dysgeusia, with the expectation of improving taste dysfunction. Background: PBM has garnered attention as a potential therapy in long COVID, a condition characterized by many persistent symptoms following the acute phase of COVID-19. Among these symptoms, dysgeusia, or altered taste perception, can significantly affect patients' quality of life. Emerging research suggests that PBM may hold promise in ameliorating dysgeusia by modulating cellular processes and reducing inflammation. Further clinical studies and randomized controlled trials are essential to establish the efficacy and safety of PBM for the treatment of dysgeusia in long COVID, but initial evidence suggests that this noninvasive modality may offer a novel avenue for symptom management. Methods: Seventy patients experiencing dysgeusia were randomly assigned to receive active local and systemic PBM (n = 34) or simulated PBM (n = 36). Low-power laser (red wavelength) was used at 18 spots on the lateral borders of the tongue (3 J per spot), salivary glands (parotid, sublingual, and submandibular glands-3 J per spot), and over the carotid artery for 10 min (60 J). Alongside laser therapy, all patients in both groups received weekly olfactory therapy for up to 8 weeks. Results: Dysgeusia improved in both groups. At weeks 7 and 8, improvement scores were significantly higher in the PBM group than in the sham group (p = 0.048). Conclusions: Combined local and systemic PBM, as applied in this study, proved effective and could serve as a viable treatment option for alleviating dysgeusia in long-COVID patients. Clinical Trial Registration: RBR-2mfbkkk.
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Affiliation(s)
- Letícia Fernandes Sobreira Parreira
- Postgraduate Program in Health Sciences, Center for Life Sciences, Pontifícia Universidade Católica de Campinas (PUC-Campinas), Campinas, Brazil
| | - Sérgio Luiz Pinheiro
- Postgraduate Program in Health Sciences, Center for Life Sciences, Pontifícia Universidade Católica de Campinas (PUC-Campinas), Campinas, Brazil
| | - Carlos Eduardo Fontana
- Postgraduate Program in Health Sciences, Center for Life Sciences, Pontifícia Universidade Católica de Campinas (PUC-Campinas), Campinas, Brazil
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Tang SW, Helmeste DM, Leonard BE. COVID-19 as a polymorphic inflammatory spectrum of diseases: a review with focus on the brain. Acta Neuropsychiatr 2023; 35:248-269. [PMID: 36861428 DOI: 10.1017/neu.2023.17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/03/2023]
Abstract
There appear to be huge variations and aberrations in the reported data in COVID-19 2 years now into the pandemic. Conflicting data exist at almost every level and also in the reported epidemiological statistics across different regions. It is becoming clear that COVID-19 is a polymorphic inflammatory spectrum of diseases, and there is a wide range of inflammation-related pathology and symptoms in those infected with the virus. The host's inflammatory response to COVID-19 appears to be determined by genetics, age, immune status, health status and stage of disease. The interplay of these factors may decide the magnitude, duration, types of pathology, symptoms and prognosis in the spectrum of COVID-19 disorders, and whether neuropsychiatric disorders continue to be significant. Early and successful management of inflammation reduces morbidity and mortality in all stages of COVID-19.
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Affiliation(s)
- Siu Wa Tang
- Department of Psychiatry, University of California, Irvine, Irvine, CA, USA
- Institute of Brain Medicine, Hong Kong, China
| | - Daiga Maret Helmeste
- Department of Psychiatry, University of California, Irvine, Irvine, CA, USA
- Institute of Brain Medicine, Hong Kong, China
| | - Brian E Leonard
- Institute of Brain Medicine, Hong Kong, China
- Department of Pharmacology, National University of Ireland, Galway, Ireland
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Wang J, Liu R, Ma H, Zhang W. The Pathogenesis of COVID-19-Related Taste Disorder and Treatments. J Dent Res 2023; 102:1191-1198. [PMID: 37729625 DOI: 10.1177/00220345231182926] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/22/2023] Open
Abstract
COVID-19, mainly manifested as acute respiratory distress syndrome, has afflicted millions of people worldwide since 2019. Taste dysfunction is a common early-stage symptom of COVID-19 infection that burdens patients for weeks or even permanently in some cases. Owing to its subjectivity and complexity, the mechanism of taste disorder is poorly studied. Previous studies have reported that the COVID-19 entry receptors are highly expressed in taste buds, thereby intensifying the cytocidal effect. Taste receptor cells are vulnerable to inflammation, and the COVID-19-induced cytokine storm causes secondary damage to taste function. Interferon and various proinflammatory cytokines can trigger cell apoptosis and disrupt the renewal of taste bud stem cells. This immune response can be further enhanced by the accumulation of Angiotensin II (Ang II) caused by an unbalanced local renin-angiotensin system (RAS) system. In addition, severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is neurotropic and can invade the brain through the olfactory bulb, affecting the nervous system. Other factors, such as host zinc deficiency, genetic susceptibility, sialic acid, and some neurotransmitters, also contribute to the pathogenesis process. Although several medical interventions have displayed effectiveness, only a few strategies exist for the treatment of postinfectious dysgeusia. Stem cell-based taste regeneration offers promise for long-term taste disorders. Clinical studies have demonstrated that stem cells can treat long COVID-19 through immune regulation. In dysgeusia, the differentiation of taste bud stem cells can be stimulated through exogenous epithelial-derived and neural-derived factors to regenerate taste buds. Tongue organoids are also emerging as functional taste buds, offering new insights into the study of taste regeneration. This review presents the current evidence of the pathogenesis of COVID-19-related dysgeusia, summarizes currently available treatments, and suggests future directions of taste regeneration therapy.
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Affiliation(s)
- J Wang
- Department of Prosthodontics, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Engineering Research Center of Advanced Dental Technology and Materials, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- National Clinical Research Center for Oral Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - R Liu
- Department of Prosthodontics, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Engineering Research Center of Advanced Dental Technology and Materials, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- National Clinical Research Center for Oral Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - H Ma
- Department of Prosthodontics, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Engineering Research Center of Advanced Dental Technology and Materials, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- National Clinical Research Center for Oral Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - W Zhang
- Department of Prosthodontics, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Engineering Research Center of Advanced Dental Technology and Materials, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- National Clinical Research Center for Oral Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Badi Y, Hammad M, Tawfik AG, Eshag MME, Elhady MM, Ragab KM, Nourelden AZ, Gamal MH, Fathallah AH. Inhaled corticosteroids' effect on COVID-19 patients: A systematic review and meta-analysis of randomized controlled trials. CANADIAN JOURNAL OF RESPIRATORY THERAPY : CJRT = REVUE CANADIENNE DE LA THERAPIE RESPIRATOIRE : RCTR 2023; 59:154-166. [PMID: 37781348 PMCID: PMC10540159 DOI: 10.29390/001c.84260] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Accepted: 07/17/2023] [Indexed: 10/03/2023]
Abstract
Background More than six million people died due to COVID-19, and 10-15% of infected individuals suffer from post-covid syndrome. Corticosteroids are widely used in the management of severe COVID-19 and post-acute COVID-19 symptoms. This study synthesizes current evidence of the effectiveness of inhaled corticosteroids (ICS) on mortality, hospital length-of-stay (LOS), and improvement of smell scores in patients with COVID-19. Methods We searched Embase, Web of Science, PubMed, Cochrane Library, and Scopus until Aug 2022. The Cochrane risk of bias tool was used to assess the quality of studies. We evaluated the effectiveness of ICS in COVID-19 patients through measures of mortality, LOS, alleviation of post-acute COVID-19 symptoms, time to sustained self-reported cure, and sense of smell (visual analog scale (VAS)). Results Ten studies were included in the meta-analysis. Our study showed a significant decrease in the LOS in ICS patients over placebo (MD = -1.52, 95% CI [-2.77 to -0.28], p-value = 0.02). Patients treated with intranasal corticosteroids (INC) showed a significant improvement in VAS smell scores from week three to week four (MD =1.52, 95% CI [0.27 to 2.78], p-value = 0.02), and alleviation of COVID-related symptoms after 14 days (RR = 1.17, 95% CI [1.09 to 1.26], p-value < 0.0001). No significant differences were detected in mortality (RR= 0.69, 95% CI [0.36 to 1.35], p-value = 0.28) and time to sustained self-reported cure (MD = -1.28, 95% CI [-6.77 to 4.20], p-value = 0.65). Conclusion We concluded that the use of ICS decreased patient LOS and improved COVID-19-related symptoms. INC may have a role in improving the smell score. Therefore, using INC and ICS for two weeks or more may prove beneficial. Current data do not demonstrate an effect on mortality or time to sustained self-reported cure. However, the evidence is inconclusive, and more studies are needed for more precise data.
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Affiliation(s)
- Yasra Badi
- All Saints University School of Medicine
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9
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Emadzadeh M, Kabiri M. Efficacy of topical steroids for the treatment of olfactory disorders caused by COVID-19: A systematic review and meta-analysis. Clin Otolaryngol 2023; 48:721-722. [PMID: 37098722 DOI: 10.1111/coa.14058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Revised: 02/27/2023] [Accepted: 03/19/2023] [Indexed: 04/27/2023]
Affiliation(s)
- Maryam Emadzadeh
- Clinical Research Development Unit, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mona Kabiri
- Clinical Research Development Unit, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran
- Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
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10
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Tsuchiya H. Treatments of COVID-19-Associated Taste and Saliva Secretory Disorders. Dent J (Basel) 2023; 11:140. [PMID: 37366663 DOI: 10.3390/dj11060140] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Revised: 05/17/2023] [Accepted: 05/23/2023] [Indexed: 06/28/2023] Open
Abstract
Since the worldwide spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, treating taste and saliva secretory disorders associated with coronavirus disease 2019 (COVID-19) has become a critical issue. The aim of the present study was to update information on treatments applicable to such oral symptoms and discuss their pathogenic mechanisms. The literature search indicated that different treatments using tetracycline, corticosteroids, zinc, stellate ganglion block, phytochemical curcumin, traditional herbal medicine, nutraceutical vitamin D, photobiomodulation, antiviral drugs, malic acid sialagogue, chewing gum, acupuncture, and/or moxibustion have potential effects on COVID-19-associated ageusia/dysgeusia/hypogeusia and xerostomia/dry mouth/hyposalivation. These treatments have multiple modes of action on viral cellular entry and replication, cell proliferation and differentiation, immunity, and/or SARS-CoV-2 infection-induced pathological conditions such as inflammation, cytokine storm, pyroptosis, neuropathy, zinc dyshomeostasis, and dysautonomia. An understanding of currently available treatment options is required for dental professionals because they may treat patients who were infected with SARS-CoV-2 or who recovered from COVID-19, and become aware of their abnormal taste and salivary secretion. By doing so, dentists and dental hygienists could play a crucial role in managing COVID-19 oral symptoms and contribute to improving the oral health-related quality of life of the relevant patients.
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Affiliation(s)
- Hironori Tsuchiya
- Department of Dental Basic Education, Asahi University School of Dentistry, Mizuho, Gifu 501-0296, Japan
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11
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Vaira LA, De Riu G, Boscolo-Rizzo P, Hopkins C, Lechien JR. In reference to Intranasal Corticosteroid Treatment on Recovery of Long-Term Olfactory Dysfunction Due to COVID-19. Laryngoscope 2023; 133:E29-E30. [PMID: 36495301 PMCID: PMC9877991 DOI: 10.1002/lary.30505] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Accepted: 09/06/2022] [Indexed: 12/14/2022]
Abstract
This is a commentary on the article by Hosseinpoor et al. Laryngoscope, 2022
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Affiliation(s)
- Luigi Angelo Vaira
- Maxillofacial Surgery Operative Unit, Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari, Italy.,Biomedical Science Department, PhD School of Biomedical Science, University of Sassari, Sassari, Italy
| | - Giacomo De Riu
- Maxillofacial Surgery Operative Unit, Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari, Italy
| | - Paolo Boscolo-Rizzo
- Department of Medical, Surgical and Health Sciences, Section of Otolaryngology, University of Trieste, Trieste, Italy
| | - Claire Hopkins
- Department of otorhinolaryngology, King's College, London, UK.,British Rhinological Society, London, UK
| | - Jerome R Lechien
- Department of Anatomy and Experimental Oncology, Mons School of Medicine, UMONS Research Institute for Health Sciences and Technology, University of Mons, Mons, Belgium.,Department of Otolaryngology-Head Neck Surgery, Elsan Polyclinic of Poitiers, Poitiers, France
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12
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Leng A, Shah M, Ahmad SA, Premraj L, Wildi K, Li Bassi G, Pardo CA, Choi A, Cho SM. Pathogenesis Underlying Neurological Manifestations of Long COVID Syndrome and Potential Therapeutics. Cells 2023; 12:816. [PMID: 36899952 PMCID: PMC10001044 DOI: 10.3390/cells12050816] [Citation(s) in RCA: 88] [Impact Index Per Article: 44.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Revised: 02/28/2023] [Accepted: 03/03/2023] [Indexed: 03/08/2023] Open
Abstract
The development of long-term symptoms of coronavirus disease 2019 (COVID-19) more than four weeks after primary infection, termed "long COVID" or post-acute sequela of COVID-19 (PASC), can implicate persistent neurological complications in up to one third of patients and present as fatigue, "brain fog", headaches, cognitive impairment, dysautonomia, neuropsychiatric symptoms, anosmia, hypogeusia, and peripheral neuropathy. Pathogenic mechanisms of these symptoms of long COVID remain largely unclear; however, several hypotheses implicate both nervous system and systemic pathogenic mechanisms such as SARS-CoV2 viral persistence and neuroinvasion, abnormal immunological response, autoimmunity, coagulopathies, and endotheliopathy. Outside of the CNS, SARS-CoV-2 can invade the support and stem cells of the olfactory epithelium leading to persistent alterations to olfactory function. SARS-CoV-2 infection may induce abnormalities in innate and adaptive immunity including monocyte expansion, T-cell exhaustion, and prolonged cytokine release, which may cause neuroinflammatory responses and microglia activation, white matter abnormalities, and microvascular changes. Additionally, microvascular clot formation can occlude capillaries and endotheliopathy, due to SARS-CoV-2 protease activity and complement activation, can contribute to hypoxic neuronal injury and blood-brain barrier dysfunction, respectively. Current therapeutics target pathological mechanisms by employing antivirals, decreasing inflammation, and promoting olfactory epithelium regeneration. Thus, from laboratory evidence and clinical trials in the literature, we sought to synthesize the pathophysiological pathways underlying neurological symptoms of long COVID and potential therapeutics.
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Affiliation(s)
- Albert Leng
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
| | - Manuj Shah
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
| | - Syed Ameen Ahmad
- Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
| | - Lavienraj Premraj
- Department of Neurology, Griffith University School of Medicine, Gold Coast, Brisbane, QLD 4215, Australia
- Critical Care Research Group, The Prince Charles Hospital, Brisbane, QLD 4032, Australia
| | - Karin Wildi
- Critical Care Research Group, The Prince Charles Hospital, Brisbane, QLD 4032, Australia
| | - Gianluigi Li Bassi
- Critical Care Research Group, The Prince Charles Hospital, Brisbane, QLD 4032, Australia
- Faculty of Medicine, University of Queensland, Brisbane, QLD 4072, Australia
- Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD 4000, Australia
- Intensive Care Unit, St Andrew’s War Memorial Hospital and the Wesley Hospital, Uniting Care Hospitals, Brisbane, QLD 4000, Australia
- Wesley Medical Research, Auchenflower, QLD 4066, Australia
| | - Carlos A. Pardo
- Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
| | - Alex Choi
- Division of Neurosciences Critical Care, Department of Neurosurgery, UT Houston, Houston, TX 77030, USA
| | - Sung-Min Cho
- Divisions of Neurosciences Critical Care and Cardiac Surgery, Departments of Neurology, Surgery, Anesthesiology and Critical Care Medicine and Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
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郑 欣, 徐 欣, 周 学, 彭 显. [Mechanisms and Management of COVID-19-Associated Taste Disorders]. SICHUAN DA XUE XUE BAO. YI XUE BAN = JOURNAL OF SICHUAN UNIVERSITY. MEDICAL SCIENCE EDITION 2023; 54:334-341. [PMID: 36949695 PMCID: PMC10409153 DOI: 10.12182/20230260306] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Indexed: 03/24/2023]
Abstract
The taste buds in the human tongue contain specialized cells that generate taste signals when they are stimulated. These signals are then transmitted to the central nervous system, allowing the human body to distinguish nutritious substances from toxic or harmful ones. This process is critical to the survival of humans and other mammals. A number of studies have shown that dysgeusia, or taste disorder, is a common complication of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which can severely affect patients' nutritional intake and quality of life. Based on the physiological process of taste perception, the direct causes of dysgeusia include dysfunction of taste receptors and damage to the taste nervous system, while indirect causes include genetic factors, aging-related changes, bacterial and viral infections, and cancer treatments such as radiotherapy and chemotherapy. The pathogenic factors of dysgeusia are complicated, further research is needed to fully understand the underlying mechanisms, and some of the reported findings and conclusions still need further validation. All these form a great challenge for clinical diagnosis of the cause and targeted treatment of dysgeusia. Herein, we reviewed published research on the physiological process of taste perception, the potential mechanisms of taste disorders related to SARS-CoV-2 infection, and strategies for prevention and treatment, providing theoretical support for establishing and improving the comprehensive management of COVID-19 complicated by taste disorders.
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Affiliation(s)
- 欣 郑
- 口腔疾病研究国家重点实验室 四川大学华西口腔医院 （成都 610041）State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - 欣 徐
- 口腔疾病研究国家重点实验室 四川大学华西口腔医院 （成都 610041）State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - 学东 周
- 口腔疾病研究国家重点实验室 四川大学华西口腔医院 （成都 610041）State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - 显 彭
- 口腔疾病研究国家重点实验室 四川大学华西口腔医院 （成都 610041）State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
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Liao B, Deng YK, Zeng M, Liu Z. Long-term Consequences of COVID-19: Chemosensory Disorders. Curr Allergy Asthma Rep 2023; 23:111-119. [PMID: 36574210 PMCID: PMC9792936 DOI: 10.1007/s11882-022-01062-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/17/2022] [Indexed: 12/28/2022]
Abstract
PURPOSE OF REVIEW A number of sequelae after acute coronavirus disease 2019 (COVID-19) significantly affect the quality of life of patients. The chemosensory disorders including olfactory dysfunction (OD) and gustatory dysfunction (GD) are two of the commonest symptoms complained by patients with COVID-19. Although chemosensory function has been reported improved in over 60% of COVID-19 patients in a short time after acute infection, it may last as a major symptom for patients with long COVID-19. This narrative review discussed current literatures on OD and GD in long COVID-19 including the prevalence, risk factors, possible mechanisms, and potential therapies. RECENT FINDINGS Although the prevalence of OD and GD has declined continuously after acute COVID-19, a considerable number of patients had persistent chemosensory disorders 3 months to 2 years after symptom onset. Female gender, initial severity of dysfunction, nasal congestion, emotional distress and depression, and SARS-CoV-2 variants have been identified as risk factors for persistent OD and GD in long COVID-19. The pathogenesis of OD and GD in long COVID-19 remains unknown, but may be analogous to the persistent OD and GD post common respiratory viral infection. Corticosteroids and olfactory training might be a potential choice regarding the treatment of lasting OD and GD after SARS-CoV-2 infection; however, more studies are needed to prove it. OD and GD are common long-term consequences of COVID-19 and influenced by gender, initial severity of dysfunction, emotional distress and depression, and SARS-CoV-2 variants. More studies are needed to illustrate their pathogenesis and to establish therapeutic strategies.
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Affiliation(s)
- Bo Liao
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030 People’s Republic of China ,Insititue of Allergy and Clinical Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China ,Hubei Clinical Research Center for Nasal Inflammatory Diseases, Wuhan, People’s Republic of China
| | - Yi-Ke Deng
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030 People’s Republic of China ,Insititue of Allergy and Clinical Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China ,Hubei Clinical Research Center for Nasal Inflammatory Diseases, Wuhan, People’s Republic of China
| | - Ming Zeng
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, People's Republic of China. .,Insititue of Allergy and Clinical Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China. .,Hubei Clinical Research Center for Nasal Inflammatory Diseases, Wuhan, People's Republic of China.
| | - Zheng Liu
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, People's Republic of China. .,Insititue of Allergy and Clinical Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China. .,Hubei Clinical Research Center for Nasal Inflammatory Diseases, Wuhan, People's Republic of China.
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Fawzy MG, Saleh H, Reda A, Bahgat EA. A green spectrophotometric method for the simultaneous determination of nasal binary mixture used in respiratory diseases: Applying isosbestic point and chemometric approaches as a resolving tool, greenness evaluation. SPECTROCHIMICA ACTA. PART A, MOLECULAR AND BIOMOLECULAR SPECTROSCOPY 2022; 283:121585. [PMID: 35988471 DOI: 10.1016/j.saa.2022.121585] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/26/2022] [Revised: 06/25/2022] [Accepted: 06/30/2022] [Indexed: 06/15/2023]
Abstract
Nasal drug combination is a very useful therapy for elevating the symptoms of various respiratory diseases as seasonal allergic rhinitis and infectious respiratory illness as pandemic COVID-19. One of best combination is Fluticasone propionate (FLU) and Azelastine (AZE). In this study, different UV spectrophotometric and chemometric methods have been applied for quantitative analysis of FLU and AZE without previous separation in their pure form, laboratory prepared mixture and pharmaceutical dosage form. Absorbance subtraction (AS) and Amplitude modulation (AM) spectrophotometric methods have been applied for the simultaneous determination of the cited drugs. Besides, three well-known chemometric techniques; namely, classical least squares (CLS), partial least square (PLS), and principal component regression (PCR) have been applied for the simultaneous analysis of both drugs by using spectrophotometric data. To be friendly to the environment, the greenness of the proposed methods was taken into consideration and evaluation of the analytical methods' greenness was done using two green analytical chemistry metrics known as, Analytical Greenness Calculator and an eco-scale scoring method. They indicated that the methods were environmentally friendly in relation to numerous approaches like instrument, reagents, and safety of waste. Analyzing laboratory prepared mixtures including different quantities of FLU and AZE, as well as their marketed dose form, was used to assess the selectivity of the applied methods. The validity of the developed methods was investigated by applying the standard addition technique. The resulting data were statistically compared to those obtained by the official or reported HPLC methods for FLU and AZE, which revealed no significant difference in accuracy and precision at p = 0.05.
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Affiliation(s)
- Michael Gamal Fawzy
- Pharmaceutical Chemistry Department, Faculty of Pharmacy, Egyptian Russian University, Badr City, Cairo 11829, Egypt.
| | - Hanaa Saleh
- Analytical Chemistry Department, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt
| | - Alaa Reda
- Pharmaceutical Chemistry Department, Faculty of Pharmacy, Egyptian Russian University, Badr City, Cairo 11829, Egypt
| | - Eman A Bahgat
- Analytical Chemistry Department, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt
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Hosseinpoor M, Kabiri M, Rajati Haghi M, Ghadam Soltani T, Rezaei A, Faghfouri A, Poustchian Gholkhatmi Z, Bakhshaee M. Intranasal Corticosteroid Treatment on Recovery of Long-Term Olfactory Dysfunction Due to COVID-19. Laryngoscope 2022; 132:2209-2216. [PMID: 36054369 PMCID: PMC9538270 DOI: 10.1002/lary.30353] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2022] [Revised: 07/13/2022] [Accepted: 08/02/2022] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIMS Olfactory dysfunction is a recognized manifestation in patients infected with Coronavirus Disease 2019 (COVID-19). This investigation aimed to assess the effect of mometasone furoate intranasal spray on the improvement of smell dysfunction in post-COVID-19 patients. MATERIALS AND METHODS This randomized placebo-controlled trial included 80 non-hospitalized adult patients who had persistent anosmia or severe microsmia for more than 4 weeks due to COVID-19 infection. The participants were randomly allocated to the intervention or placebo group to receive mometasone furoate nasal spray or sodium chloride intranasal spray during 4 weeks of follow-up, respectively. The patients' olfactory dysfunction was assessed in terms of visual analog scale (VAS), and smell test score according to the modified version of the University of Pennsylvania smell identification test for the Iranian population. RESULTS A total of 70 participants completed the follow-up period and were analyzed in this study. By comparing the olfactory scores including smell test and VAS scores, no significant differences were found between case and control groups at baseline, 2, and 4 weeks intervals. However, the change of both olfactory scores at pre to post-treatment intervals and 2-4 weeks was significantly higher in the mometasone group relative to the placebo group. At post-treatment, the frequency of anosmia was 22.9% reduced in the case group compared to the control group. CONCLUSION Overall, there was no significant difference in olfactory dysfunction between the two groups during follow-up. However, based on the significant between-group difference in terms of olfactory scores changes, it seems that the nasal corticosteroids may be a positive effect on the recovery process of patients who received more than 2 weeks. LEVEL OF EVIDENCE 2 Laryngoscope, 132:2209-2216, 2022.
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Affiliation(s)
- Masoumeh Hosseinpoor
- Sinus and Surgical Endoscopic Research CenterMashhad University of Medical SciencesMashhadIran
| | - Mona Kabiri
- Clinical Research Development Unit, Ghaem Hospital, Faculty of MedicineMashhad University of Medical SciencesMashhadIran
| | - Mohsen Rajati Haghi
- Department of Otorhinolaryngology, Sinus and Surgical Endoscopic Research CenterMashhad University of Medical SciencesMashhadIran
| | | | - Alireza Rezaei
- Department of Pathology, Mashhad BranchIslamic Azad University of Medical SciencesMashhadIran
| | - Atiyeh Faghfouri
- Student Research Committee, Faculty of MedicineMashhad University of Medical SciencesMashhadIran
| | | | - Mehdi Bakhshaee
- Department of Otorhinolaryngology, Sinus and Surgical Endoscopic Research CenterMashhad University of Medical SciencesMashhadIran
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Khurana K, Singh CV. Management of Anosmia in COVID-19: A Comprehensive Review. Cureus 2022; 14:e30425. [PMID: 36407192 PMCID: PMC9670825 DOI: 10.7759/cureus.30425] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Accepted: 10/18/2022] [Indexed: 11/07/2022] Open
Abstract
With the evolving understanding of COVID-19, a thorough analysis of the effects of this unique coronavirus on the affected people's olfactory abilities could highlight the disease's specific course of treatment. Researchers have discovered that the neurological side effects of SARS-CoV-2 infection include acute anosmia and ageusia. This work aims to review the relevant mechanisms, provide information on COVID-19-related anosmia, and suggest a novel approach to treating long-term anosmia brought on by coronavirus disease. For that, we did a thorough literature assessment of the subject from various online resources, including PubMed, Scopus, and Google Scholar. We evaluated the publications that described anosmia in COVID-19 and its management. In patients with SARS-CoV-2 infections, the angiotensin-converting enzyme two receptor plays a crucial role in the anosmia process. Olfactory systems are directly harmed by new coronaviruses when they connect with sustentacular cells' ACE-2 (Angiotensin converting enzyme-2) receptors. Other suggested processes include the virus's infiltration of the olfactory nerve and the ensuing local inflammation. Therefore, neuroprotective, anti-inflammatory, or depolarizing medications may be helpful for COVID-19 individuals who have lost their sense of smell. According to the available data, we found out olfactory training, topical or oral corticosteroids, caffeine, insulin, or minocycline may effectively treat COVID-19 odor loss. A novel method of treating long-term COVID-19 with persistent anosmia can be suggested based on recent investigations. The path to effective anosmia management is still somewhat hazy, but there is hope that we can find the right treatment plan with the right clinical trials and additional research. People who lost their sense of smell during COVID-19 can be reassured that recovery is typically possible.
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da Silva Júnior RT, Santos Apolonio J, Cuzzuol BR, da Costa BT, Silva CS, Araújo GRL, Silva Luz M, Marques HS, Santos LKDS, Pinheiro SLR, Lima de Souza Gonçalves V, Calmon MS, Freire de Melo F. COVID-19 neuropsychiatric repercussions: Current evidence on the subject. World J Methodol 2022; 12:365-380. [PMID: 36186752 PMCID: PMC9516547 DOI: 10.5662/wjm.v12.i5.365] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 06/30/2022] [Accepted: 07/25/2022] [Indexed: 02/07/2023] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has affected the entire world, causing the coronavirus disease 2019 (COVID-19) pandemic since it was first discovered in Wuhan, China in December 2019. Among the clinical presentation of the disease, in addition to fever, fatigue, cough, dyspnea, diarrhea, nausea, vomiting, and abdominal pain, infected patients may also experience neurological and psychiatric repercussions during the course of the disease and as a post-COVID-19 sequelae. Thus, headache, dizziness, olfactory and gustatory dysfunction, cerebrovascular disorders, neuromuscular abnormalities, anxiety, depression, and post-traumatic stress disorder can occur both from the infection itself and from social distancing and quarantine. According to current evidence about this infection, the virus has the ability to infect the central nervous system (CNS) via angiotensin-converting enzyme 2 (ACE2) receptors on host cells. Several studies have shown the presence of ACE2 in nerve cells and nasal mucosa, as well as transmembrane serine protease 2, key points for interaction with the viral Spike glycoprotein and entry into the CNS, being olfactory tract and blood-brain barrier, through hematogenous dissemination, potential pathways. Thus, the presence of SARS-CoV-2 in the CNS supports the development of neuropsychiatric symptoms. The management of these manifestations seems more complex, given that the dense parenchyma and impermeability of brain tissue, despite protecting the brain from the infectious process, may hinder virus elimination. Still, some alternatives used in non-COVID-19 situations may lead to worse prognosis of acute respiratory syndrome, requiring caution. Therefore, the aim of this review is to bring more current points related to this infection in the CNS, as well as the repercussions of the isolation involved by the pandemic and to present perspectives on interventions in this scenario.
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Affiliation(s)
| | - Jonathan Santos Apolonio
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029094, Brazil
| | - Beatriz Rocha Cuzzuol
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029094, Brazil
| | - Bruna Teixeira da Costa
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029094, Brazil
| | - Camilo Santana Silva
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029094, Brazil
| | - Glauber Rocha Lima Araújo
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029094, Brazil
| | - Marcel Silva Luz
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029094, Brazil
| | - Hanna Santos Marques
- Universidade Estadual do Sudoeste da Bahia, Universidade Estadual do Sudoeste da Bahia, Vitória da Conquista 45083900, Brazil
| | - Luana Kauany de Sá Santos
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029094, Brazil
| | - Samuel Luca Rocha Pinheiro
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029094, Brazil
| | | | - Mariana Santos Calmon
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029094, Brazil
| | - Fabrício Freire de Melo
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029094, Brazil
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O'Byrne L, Webster KE, MacKeith S, Philpott C, Hopkins C, Burton MJ. Interventions for the treatment of persistent post-COVID-19 olfactory dysfunction. Cochrane Database Syst Rev 2022; 9:CD013876. [PMID: 36062970 PMCID: PMC9443431 DOI: 10.1002/14651858.cd013876.pub3] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
BACKGROUND Olfactory dysfunction is a common consequence of COVID-19 infection and persistent symptoms can have a profound impact on quality of life. At present there is little guidance on how best to treat this condition. A variety of interventions have been suggested to promote recovery, including medication and olfactory training. However, it is uncertain whether any intervention is of benefit. This is an update of the 2021 review with one additional study added. OBJECTIVES: 1) To evaluate the benefits and harms of any intervention versus no treatment for people with persisting olfactory dysfunction due to COVID-19 infection. 2) To keep the evidence up-to-date, using a living systematic review approach. SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the latest search was 20 October 2021. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in people with COVID-19 related olfactory disturbance that had persisted for at least four weeks. We included any intervention compared to no treatment or placebo. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were the recovery of sense of smell, disease-related quality of life and serious adverse effects. Secondary outcomes were the change in sense of smell, general quality of life, prevalence of parosmia and other adverse effects (including nosebleeds/bloody discharge). We used GRADE to assess the certainty of the evidence for each outcome. MAIN RESULTS We included two studies with 30 participants. The studies evaluated the following interventions: systemic corticosteroids plus intranasal corticosteroid/mucolytic/decongestant and palmitoylethanolamide plus luteolin. Systemic corticosteroids plus intranasal corticosteroid/mucolytic/decongestant compared to no intervention We included a single RCT with 18 participants who had anosmia for at least 30 days following COVID-19 infection. Participants received a 15-day course of oral corticosteroids combined with nasal irrigation (consisting of an intranasal corticosteroid/mucolytic/decongestant solution) or no intervention. Psychophysical testing was used to assess olfactory function at 40 days. This is a single, small study and for all outcomes the certainty of evidence was very low. We are unable to draw meaningful conclusions from the numerical results. Palmitoylethanolamide plus luteolin compared to no intervention We included a single RCT with 12 participants who had anosmia or hyposmia for at least 90 days following COVID-19 infection. Participants received a 30-day course of palmitoylethanolamide and luteolin or no intervention. Psychophysical testing was used to assess olfactory function at 30 days. This is a single, small study and for all outcomes the certainty of evidence was very low. We are unable to draw meaningful conclusions from the numerical results. AUTHORS' CONCLUSIONS There is very limited evidence available on the efficacy and harms of treatments for persistent olfactory dysfunction following COVID-19 infection. However, we have identified a number of ongoing trials in this area. As this is a living systematic review we will update the data regularly, as new results become available.
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Affiliation(s)
- Lisa O'Byrne
- Department of Otolaryngology Head and Neck Surgery, St Vincent's University Hospital, Dublin 4, Ireland
| | - Katie E Webster
- Cochrane ENT, Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK
| | - Samuel MacKeith
- Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - Carl Philpott
- Department of Medicine, Norwich Medical School, University of East Anglia, Norwich, UK
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Webster KE, O'Byrne L, MacKeith S, Philpott C, Hopkins C, Burton MJ. Interventions for the prevention of persistent post-COVID-19 olfactory dysfunction. Cochrane Database Syst Rev 2022; 9:CD013877. [PMID: 36063364 PMCID: PMC9443936 DOI: 10.1002/14651858.cd013877.pub3] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Loss of olfactory function is well recognised as a symptom of COVID-19 infection, and the pandemic has resulted in a large number of individuals with abnormalities in their sense of smell. For many, the condition is temporary and resolves within two to four weeks. However, in a significant minority the symptoms persist. At present, it is not known whether early intervention with any form of treatment (such as medication or olfactory training) can promote recovery and prevent persisting olfactory disturbance. This is an update of the 2021 review with four studies added. OBJECTIVES 1) To evaluate the benefits and harms of any intervention versus no treatment for people with acute olfactory dysfunction due to COVID-19 infection. 2) To keep the evidence up-to-date, using a living systematic review approach. SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the latest search was 20 October 2021. SELECTION CRITERIA We included randomised controlled trials (RCTs) in people with COVID-19 related olfactory disturbance, which had been present for less than four weeks. We included any intervention compared to no treatment or placebo. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were the presence of normal olfactory function, serious adverse effects and change in sense of smell. Secondary outcomes were the prevalence of parosmia, change in sense of taste, disease-related quality of life and other adverse effects (including nosebleeds/bloody discharge). We used GRADE to assess the certainty of the evidence for each outcome. MAIN RESULTS: We included five studies with 691 participants. The studies evaluated the following interventions: intranasal corticosteroid sprays, intranasal corticosteroid drops, intranasal hypertonic saline and zinc sulphate. Intranasal corticosteroid spray compared to no intervention/placebo We included three studies with 288 participants who had olfactory dysfunction for less than four weeks following COVID-19. Presence of normal olfactory function The evidence is very uncertain about the effect of intranasal corticosteroid spray on both self-rated recovery of olfactory function and recovery of olfactory function using psychophysical tests at up to four weeks follow-up (self-rated: risk ratio (RR) 1.19, 95% confidence interval (CI) 0.85 to 1.68; 1 study; 100 participants; psychophysical testing: RR 2.3, 95% CI 1.16 to 4.63; 1 study; 77 participants; very low-certainty evidence). Change in sense of smell The evidence is also very uncertain about the effect of intranasal corticosteroid spray on self-rated change in the sense of smell (at less than 4 weeks: mean difference (MD) 0.5 points lower, 95% CI 1.38 lower to 0.38 higher; 1 study; 77 participants; at > 4 weeks to 3 months: MD 2.4 points higher, 95% CI 1.32 higher to 3.48 higher; 1 study; 100 participants; very low-certainty evidence, rated on a scale of 1 to 10, higher scores mean better olfactory function). Intranasal corticosteroids may make little or no difference to the change in sense of smell when assessed with psychophysical testing (MD 0.2 points, 95% CI 2.06 points lower to 2.06 points higher; 1 study; 77 participants; low-certainty evidence, 0- to 24-point scale, higher scores mean better olfactory function). Serious adverse effects The authors of one study reported no adverse effects, but their intention to collect these data was not pre-specified so we are uncertain if these were systematically sought and identified. The remaining two studies did not report on adverse effects. Intranasal corticosteroid drops compared to no intervention/placebo We included one study with 248 participants who had olfactory dysfunction for ≤ 15 days following COVID-19. Presence of normal olfactory function Intranasal corticosteroid drops may make little or no difference to self-rated recovery at > 4 weeks to 3 months (RR 1.00, 95% CI 0.89 to 1.11; 1 study; 248 participants; low-certainty evidence). No other outcomes were assessed by this study. Data on the use of hypertonic saline nasal irrigation and the use of zinc sulphate to prevent persistent olfactory dysfunction are included in the full text of the review. AUTHORS' CONCLUSIONS There is very limited evidence available on the efficacy and harms of treatments for preventing persistent olfactory dysfunction following COVID-19 infection. However, we have identified a number of ongoing trials in this area. As this is a living systematic review we will update the data regularly, as new results become available.
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Affiliation(s)
- Katie E Webster
- Cochrane ENT, Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK
| | - Lisa O'Byrne
- Department of Otolaryngology Head and Neck Surgery, St Vincent's University Hospital, Dublin 4, Ireland
| | - Samuel MacKeith
- Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - Carl Philpott
- Department of Medicine, Norwich Medical School, University of East Anglia, Norwich, UK
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21
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Narayanan SN, Shivappa P, Padiyath S, Bhaskar A, Li YW, Merghani TH. The Prevalence and Pathophysiology of Chemical Sense Disorder Caused by the Novel Coronavirus. Front Public Health 2022; 10:839182. [PMID: 35734755 PMCID: PMC9207763 DOI: 10.3389/fpubh.2022.839182] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2021] [Accepted: 04/20/2022] [Indexed: 12/27/2022] Open
Abstract
Emerging viral infections are a ceaseless challenge and remain a global public health concern. The world has not yet come back to normal from the devastating effects of the highly contagious and pathogenic novel coronavirus, or Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Olfactory and taste dysfunction is common in patients infected by the novel coronavirus. In light of the emergence of different coronavirus variants, it is important to update the prevalence and pathophysiology of these side effects. In this review, articles published on the prevalence of olfactory and taste dysfunction from coronavirus disease (COVID-19) and their possible pathophysiologic mechanisms have been reviewed and reported. The modulatory role of different SARS-CoV-2 variants on the chemical senses is then described. The clinical relevance of chemical sense disorder and its long-term morbidity and management is also discussed.
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Affiliation(s)
- Sareesh Naduvil Narayanan
- Department of Physiology, Ras Al Khaimah College of Medical Sciences, Ras Al Khaimah Medical and Health Sciences University, Ras Al Khaimah, United Arab Emirates
- *Correspondence: Sareesh Naduvil Narayanan ; orcid.org/0000-0002-2980-2352
| | - Pooja Shivappa
- Department of Basic Sciences, Ras Al Khaimah College of Medical Sciences, Ras Al Khaimah Medical and Health Sciences University, Ras Al Khaimah, United Arab Emirates
| | - Sreeshma Padiyath
- Independent Microbiology Researcher, Ras Al Khaimah, United Arab Emirates
| | - Anand Bhaskar
- Department of Biomedical Sciences, Faculty of Medicine, Macau University of Science and Technology, Taipa, Macau SAR, China
| | - Yan Wa Li
- Department of Biomedical Sciences, Faculty of Medicine, Macau University of Science and Technology, Taipa, Macau SAR, China
| | - Tarig Hakim Merghani
- Department of Physiology, Ras Al Khaimah College of Medical Sciences, Ras Al Khaimah Medical and Health Sciences University, Ras Al Khaimah, United Arab Emirates
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22
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Alrasheedi A. Characterization, treatment modalities, and self-perceived improvement of post-COVID-19 phantosmia: a case series of eleven patients. RHINOLOGY ONLINE 2022. [DOI: 10.4193/rhinol/22.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022] Open
Abstract
Background: Loss of smell and taste is one of the early and sensitive symptoms of COVID-19 that usually improves over time. Post-COVID-19 phantosmia, a smell distorted sensation without the presence of odorants, has deleterious and long-lasting effects on the patient's quality of life. We aimed to present our experience with phantosmia. Case presentations: We report a description of a series of eleven cases (age of 29 ± 9 years, and 54.5% females) of post-COVID-19 phantosmia without any other comorbidity, and the effects of combined treatment modalities (olfactory training, nasal irrigation with budesonide and oral prednisolone) on self-perceived improvement in phantosmia. Conclusions: We postulate that the combined 10 days oral prednisolone, smell training, and nasal irrigation for three months improved post-COVID-19 phantosmia assessed as post vs. pre self-perceived improvement, although this was not aimed at as a treatment since it was not compared to untreated controls.
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23
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McCarthy MW. Current and emerging immunomodulators for treatment of SARS-CoV2 infection (COVID-19). Expert Opin Pharmacother 2022; 23:623-628. [PMID: 35103549 PMCID: PMC8862166 DOI: 10.1080/14656566.2022.2035360] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Accepted: 01/25/2022] [Indexed: 12/15/2022]
Abstract
INTRODUCTION SARS-CoV-2, the virus that causes COVID-19, elicits a variety of host responses ranging from asymptomatic or mild illness in most people, to severe disease and critical illness in a subset of patients with systemic inflammation and hypoxemic respiratory failure. AREAS COVERED Heterogeneous clinical presentations are often driven by disparate responses of the host immune system, with severe disease associated with aberrant interferon signaling or cytokine storm syndrome. This manuscript examines current therapeutic approaches, including the use of immunomodulators such as corticosteroids, interleukin inhibitors, kinase inhibitors, fluvoxamine, and ivermectin, and also explores the ways that these therapies and others may be used to treat COVID-19 in the future. EXPERT OPINION Modulation of the immune response has become a mainstay of treatment of COVID-19, although the optimal mechanism has not yet been defined and there is considerable controversy regarding clinical management. As time progresses, the therapeutic approach to COVID-19 will undoubtedly change, particularly as we learn more about the pathophysiology of SARS-CoV-2 infection.
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Affiliation(s)
- Matthew W. McCarthy
- Weill Cornell Medicine, Division of General Internal Medicine, New York, NY, USA
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24
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Systematic review and meta-analysis of olfactory and gustatory dysfunction in COVID-19. Int J Infect Dis 2022; 117:155-161. [PMID: 35134561 PMCID: PMC8817419 DOI: 10.1016/j.ijid.2022.02.004] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Revised: 01/31/2022] [Accepted: 02/01/2022] [Indexed: 12/20/2022] Open
Abstract
Background Chemosensory disorders associated with COVID-19 have been widely discussed during the pandemic. We performed a meta-analysis to assess the risk factors for olfactory and gustatory dysfunction in patients with COVID-19. Methods Three databases (PubMed, Embase, and Cochrane Library) were searched for studies published between December 1, 2019, and August 31, 2021. We selected random-effects model or fixed-effects model to pool data based on heterogeneity. The results were reported as odds ratios (ORs) or standardized mean differences (SMDs) and the corresponding 95% confidence intervals (CIs). Heterogeneity was reported as I2. Results Twenty-six studies with a total of 13,813 patients were included. The pooled data indicated that sex (OR 1.47; 95% CI 0.93–2.31), age (SMD −5.80; 95% CI −13.35 to 1.75), smoking (OR 2.04; 95% CI 0.72–5.79), and comorbidity (OR 1.21; 95% CI 0.58–2.53) of patients with COVID-19 had no effect on gustatory dysfunction. Olfactory dysfunction was more likely to occur in older patients with COVID-19 (SMD, −5.22; 95% CI, −8.28 to −2.16). Patients with COVID-19 with nasal congestion (OR 3.41; 95% CI 2.30–5.06) and rhinorrhea (OR 2.35; 95% CI 1.60–3.45) were more prone to olfactory dysfunction. Conclusion These findings emphasize that older patients with COVID-19 are more likely to experience olfactory dysfunction. Symptoms of nasal congestion and rhinorrhea may affect the recognition of olfactory dysfunction.
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25
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Wu TJ, Yu AC, Lee JT. Management of post-COVID-19 olfactory dysfunction. CURRENT TREATMENT OPTIONS IN ALLERGY 2022; 9:1-18. [PMID: 35004126 PMCID: PMC8723803 DOI: 10.1007/s40521-021-00297-9] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/18/2021] [Indexed: 01/02/2023]
Abstract
Purpose of Review Olfactory dysfunction is a frequent complication of SARS-CoV-2 infection. This review presents the current literature regarding the management of post-COVID-19 olfactory dysfunction (PCOD). Recent Findings A systematic review of the literature using the PubMed/MEDLINE, EMBASE, and Cochrane databases for the following keywords, “Covid-19,” “SARS-CoV-2,” “anosmia,” “olfactory,” “treatment,” and “management” was performed. While most cases of post-COVID-19 olfactory dysfunction resolve spontaneously within 2 weeks of symptom onset, patients with symptoms that persist past 2 weeks require medical management. The intervention with the greatest degree of supporting evidence is olfactory training, wherein patients are repeatedly exposed to potent olfactory stimuli. To date, no large-scale randomized clinical trials exist that examine the efficacy of pharmacologic therapies for PCOD. Limited clinical trials and prospective controlled trials suggest intranasal corticosteroids and oral corticosteroids may alleviate symptoms. Summary Olfactory training should be initiated as soon as possible for patients with PCOD. Patients may benefit from a limited intranasal or oral corticosteroid course. Further research on effective pharmacologic therapies for PCOD is required to manage the growing number of patients with this condition.
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Affiliation(s)
- Tara J Wu
- Department of Head and Neck Surgery, David Geffen School of Medicine at the University of California, Los Angeles (UCLA), 10833 Le Conte Avenue, 62-132 CHS, Los Angeles, CA 90095 USA
| | - Alice C Yu
- Department of Head and Neck Surgery, David Geffen School of Medicine at the University of California, Los Angeles (UCLA), 10833 Le Conte Avenue, 62-132 CHS, Los Angeles, CA 90095 USA
| | - Jivianne T Lee
- Department of Head and Neck Surgery, David Geffen School of Medicine at the University of California, Los Angeles (UCLA), 10833 Le Conte Avenue, 62-132 CHS, Los Angeles, CA 90095 USA
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26
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Damnjanović B, Stanisavljević J, Šijan Đ, Rović I, Jovanović N, Milenković M. Intensive care therapy during the pandemic in 2020 and beyond: Mnemonics can help. SERBIAN JOURNAL OF ANESTHESIA AND INTENSIVE THERAPY 2022. [DOI: 10.5937/sjait2206095d] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
In a busy working environment, with a shortage of healthcare workers and increased workloads since the beginning of the COVID-19 pandemic, the implementation of an easy-to-remember mnemonic can significantly help anesthesiologists and clinicians in conducting intensive therapy. One of the first mnemonics in critical care therapy was implemented by Jean-Louis Vincent in 2005. FAST HUG concept reminds clinicians of crucial moments in therapy - nutritional support(F-feeding), analgesia and sedation (A - analgesia, S - sedation), thrombosis prophylaxis (T - thrombolytic prophylaxis), head elevation in bed (H - head of the elevated bed), antiulcer therapy (U - stress ulcer prevention) and glycemic control (G - glucose control). This acronym has been modified and tested in several studies over the years for the treatment of different patient types. This concept is widely utilized in intensive care units, it is characterized with easy implementation, and proved to be useful in ventilator-associated pneumonia prevention. Therapy of critically ill patients with COVID-19 is based on elements of general intensive care therapy with some specific therapeutic guidelines. With the intention to ease and improve therapy of patients with COVID-19 in intensive care units, a new and comprehensive acronym is proposed: One Fast Hug Bids COVID.
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27
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Khani E, Khiali S, Beheshtirouy S, Entezari-Maleki T. Potential pharmacologic treatments for COVID-19 smell and taste loss: A comprehensive review. Eur J Pharmacol 2021; 912:174582. [PMID: 34678243 PMCID: PMC8524700 DOI: 10.1016/j.ejphar.2021.174582] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Revised: 10/08/2021] [Accepted: 10/18/2021] [Indexed: 12/30/2022]
Abstract
The acute loss of taste and smell following COVID-19 are hallmark symptoms that affect 20-85% of patients. However, the pathophysiology and potential treatments of COVID-19 smell and taste loss are not fully understood. We searched the literature to review the potential pathologic pathways and treatment options for COVID-19 smell and taste loss. The interaction of novel coronavirus with ACE-2 receptors expressed on sustentacular cells and taste buds results in direct damage to the olfactory and gustatory systems. Also, the invasion of the virus to the olfactory neurons and consequent local inflammation are other proposed mechanisms. Therefore, COVID-19 patients with smell or taste loss may benefit from neuroprotective, anti-inflammatory, or depolarizing agents. Based on the current evidence, phosphodiesterase inhibitors, insulin, and corticosteroids can be promising for the management of COVID-19 smell and taste loss. This review provided crucial information for treating COVID-19-related smell and/or taste loss, urging to perform large clinical trials to find optimum treatment options.
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Affiliation(s)
- Elnaz Khani
- Department of Clinical Pharmacy, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Sajad Khiali
- Department of Clinical Pharmacy, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Samineh Beheshtirouy
- Department of Clinical Pharmacy, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Taher Entezari-Maleki
- Department of Clinical Pharmacy, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran,Cardiovascular Research Center, Tabriz University of Medical Sciences, Tabriz, Iran,Corresponding author. Department of Clinical Pharmacy, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, P.O. Box: 51664-14766 12, Iran
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28
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Lechien JR, Saussez S, Maniaci A, Vaira LA. The study of recovery rates of COVID-19 olfactory and gustatory dysfunctions requires psychophysical evaluations. Am J Otolaryngol 2021; 42:103168. [PMID: 34339959 PMCID: PMC8320430 DOI: 10.1016/j.amjoto.2021.103168] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2021] [Accepted: 05/25/2021] [Indexed: 01/12/2023]
Affiliation(s)
- Jerome R Lechien
- COVID-19 Task Force of the Young-Otolaryngologists of the International Federations of Oto-rhino-laryngological Societies (YO-IFOS), Paris, France; Department of Human Anatomy and Experimental Oncology, Faculty of Medicine, UMONS Research Institute for Health Sciences and Technology, University of Mons (UMons), Mons, Belgium; Department of Otorhinolaryngology and Head and Neck Surgery, CHU de Bruxelles, CHU Saint-Pierre, School of Medicine, Université Libre de Bruxelles, Brussels, Belgium; Department of Otolaryngology-Head & Neck Surgery, Foch Hospital, School of Medicine, UFR Simone Veil, Université Versailles Saint-Quentin-en-Yvelines (Paris Saclay University), Paris, France.
| | - Sven Saussez
- COVID-19 Task Force of the Young-Otolaryngologists of the International Federations of Oto-rhino-laryngological Societies (YO-IFOS), Paris, France; Department of Human Anatomy and Experimental Oncology, Faculty of Medicine, UMONS Research Institute for Health Sciences and Technology, University of Mons (UMons), Mons, Belgium; Department of Otorhinolaryngology and Head and Neck Surgery, CHU de Bruxelles, CHU Saint-Pierre, School of Medicine, Université Libre de Bruxelles, Brussels, Belgium
| | - Antonino Maniaci
- COVID-19 Task Force of the Young-Otolaryngologists of the International Federations of Oto-rhino-laryngological Societies (YO-IFOS), Paris, France; Department of Medical and Surgical Sciences and Advanced Technologies G.F. Ingrassia, ENT Section, University of Catania, Catania, Italy
| | - Luigi A Vaira
- COVID-19 Task Force of the Young-Otolaryngologists of the International Federations of Oto-rhino-laryngological Societies (YO-IFOS), Paris, France; Maxillofacial Surgery Operative Unit, Department of Medical, Surgical and Experimental Sciences, University of Sassari, Italy; Biomedical Science PhD School, Biomedical Science Department, University of Sassari, Italy
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29
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Najafloo R, Majidi J, Asghari A, Aleemardani M, Kamrava SK, Simorgh S, Seifalian A, Bagher Z, Seifalian AM. Mechanism of Anosmia Caused by Symptoms of COVID-19 and Emerging Treatments. ACS Chem Neurosci 2021; 12:3795-3805. [PMID: 34609841 PMCID: PMC8507153 DOI: 10.1021/acschemneuro.1c00477] [Citation(s) in RCA: 59] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Accepted: 09/20/2021] [Indexed: 01/08/2023] Open
Abstract
The occurrence of anosmia, the loss or change in sense of smell, is one of the most common symptoms of COVID-19 experienced by almost 53% of those affected. Several hypotheses explain the mechanism of anosmia in patients suffering from COVID-19. This study aims to review the related mechanisms and answer the questions regarding COVID-19-related anosmia as well as propose a new strategy for treatment of long-term anosmia as a result of COVID-19 infection. This paper covers all of the studies investigating olfactory disorders following COVID-19 infection and explains the possible reasons for the correlated anosmia, including olfactory cleft syndrome, local inflammation in the nasal epithelium, early apoptosis of olfactory cells, changes in olfactory cilia and odor transmission, damage to microglial cells, effect on olfactory bulbs, epithelial olfactory injury, and impairment of olfactory neurons and stem cells. The key questions that arise in this field have been discussed, such as why prevalent anosmia is varied among the age categories and among sexes and the correlation of anosmia with mild or severe COVID-19 infection. The angiotensin-converting enzyme 2 receptor is a significant player in the mechanism of anosmia in COVID-19 patients. Based on current studies, a novel approach to treat long-COVID-19 with ongoing anosmia has been proposed. The fields of smart drug delivery, tissue engineering, and cell therapy provide a hypothesized strategy that can minimize the side effects of current treatments and support efficient recovery of the olfactory system.
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Affiliation(s)
- Raziyeh Najafloo
- Department
of Tissue Engineering & Regenerative Medicine, Faculty of Advanced
Technologies in Medicine, Iran University
of Medical Sciences (IUMS), Tehran 1449614535, Iran
| | - Jila Majidi
- Department
of Tissue Engineering & Regenerative Medicine, Faculty of Advanced
Technologies in Medicine, Iran University
of Medical Sciences (IUMS), Tehran 1449614535, Iran
| | - Alimohamad Asghari
- Skull
Base Research Center, Hazrat Rasoul Akram Hospital, The Five Senses
Health Institute, Iran University of Medical
Sciences (IUMS), Tehran 1445613131, Iran
| | - Mina Aleemardani
- Biomaterials
and Tissue Engineering Group, Department of Materials Science and
Engineering, Kroto Research Institute, The
University of Sheffield, Sheffield S3 7HQ, United Kingdom
| | - Seyed Kamran Kamrava
- ENT
and Head and Neck Research Center and Department, Hazrat Rasoul Akram
Hospital, The Five Senses Health Institute, Iran University of Medical Sciences (IUMS), Tehran 1445613131, Iran
| | - Sara Simorgh
- Department
of Tissue Engineering & Regenerative Medicine, Faculty of Advanced
Technologies in Medicine, Iran University
of Medical Sciences (IUMS), Tehran 1449614535, Iran
| | - Amelia Seifalian
- University
College London Medical School (UCL), London WC1E 6BT, United
Kingdom
- Watford
General Hospital, Watford WD18 0HB, United Kingdom
| | - Zohreh Bagher
- Department
of Tissue Engineering & Regenerative Medicine, Faculty of Advanced
Technologies in Medicine, Iran University
of Medical Sciences (IUMS), Tehran 1449614535, Iran
- ENT
and Head and Neck Research Center and Department, Hazrat Rasoul Akram
Hospital, The Five Senses Health Institute, Iran University of Medical Sciences (IUMS), Tehran 1445613131, Iran
| | - Alexander M. Seifalian
- Nanotechnology
and Regenerative Medicine Commercialisation Centre (NanoRegMed Ltd.), London BioScience Innovation Centre, London NW1 0NH, United Kingdom
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30
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Treatment and Prognosis of COVID-19 Associated Olfactory and Gustatory Dysfunctions. J Pers Med 2021; 11:jpm11101037. [PMID: 34683178 PMCID: PMC8539133 DOI: 10.3390/jpm11101037] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2021] [Revised: 09/14/2021] [Accepted: 10/14/2021] [Indexed: 01/08/2023] Open
Abstract
Olfactory and gustatory dysfunctions are important initial symptoms of coronavirus disease 2019 (COVID-19). However, the treatment modality for these conditions has yet to be clearly established. Therefore, most physicians have been administering empirical treatments for COVID-19-associated olfactory dysfunction, including topical or systemic steroid supplementation and olfactory training. In this literature review, we summarize the clinical course and effects of various treatments currently being conducted in patients with COVID-19-associated olfactory and gustatory dysfunctions.
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31
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Peterson CJ, Sarangi A, Bangash F. Neurological sequelae of COVID-19: a review. THE EGYPTIAN JOURNAL OF NEUROLOGY, PSYCHIATRY AND NEUROSURGERY 2021; 57:122. [PMID: 34511868 PMCID: PMC8424148 DOI: 10.1186/s41983-021-00379-0] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Accepted: 08/26/2021] [Indexed: 01/28/2023] Open
Abstract
Background The COVID-19 pandemic has produced a myriad of challenges, including identifying and treating neurological sequelae. Main body COVID-19 can cause olfactory and respiratory dysfunction with average recovery within 1 month and a minority of patients experiencing symptoms at 8-month follow-up. Headaches are also very common (up to 93%) amongst patients with persistent COVID-19 symptoms. COVID-19 illness may also affect cognition, although results are mixed. Conclusion While many studies have focused on acute COVID-19 symptoms, more longitudinal studies will need to assess the neurological sequelae of the disease. Furthermore, care must be taken when attributing sequelae to COVID-19 illness and not an unrelated cause. Finally, there is concern that COVID-19 may be associated with secondary illnesses, such as Guillain–Barre, and may even contribute to the development of diseases, such as Alzheimer’s.
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Affiliation(s)
- Christopher J Peterson
- Menninger Department of Psychiatry, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030 USA
| | - Ashish Sarangi
- Department of Psychiatry, Texas Tech University Health Sciences Center, 3601 4th St., Lubbock, TX 79430 USA
| | - Fariha Bangash
- SUNY Upstate Medical University, 750E Adams St, Syracuse, NY 13210 USA
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32
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Olfactory dysfunction at six months after coronavirus disease 2019 infection. The Journal of Laryngology & Otology 2021; 135:839-843. [PMID: 34348821 PMCID: PMC8367869 DOI: 10.1017/s0022215121002085] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Objective This study aimed to assess olfactory dysfunction in patients at six months after confirmed coronavirus disease 2019 infection. Methods Coronavirus disease 2019 positive patients were assessed six months following diagnosis. Patient data were recoded as part of the adapted International Severe Acute Respiratory and Emerging Infection Consortium Protocol. Olfactory dysfunction was assessed using the University of Pennsylvania Smell Identification Test. Results Fifty-six patients were included. At six months after coronavirus disease 2019 diagnosis, 64.3 per cent of patients (n = 36) were normosmic, 28.6 per cent (n = 16) had mild to moderate microsmia and 7 per cent (n = 4) had severe microsmia or anosmia. There was a statistically significant association between older age and olfactory dysfunction. Hospital or intensive care unit admission did not lead to worse olfactory outcomes compared to those managed in the out-patient setting. Conclusion At six months after coronavirus disease 2019 diagnosis, approximately two-thirds of patients will be normosmic. This study is the first to describe six-month outcomes for post-coronavirus disease 2019 patients in terms of olfactory dysfunction.
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33
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Singh CV, Jain S, Parveen S, Deshmukh P. The outcome of fluticasone nasal spray on anosmia and triamcinolone oral paste in taste dysgeusia in COVID-19 patients. Am J Otolaryngol 2021; 42:103009. [PMID: 33846030 PMCID: PMC8019654 DOI: 10.1016/j.amjoto.2021.103009] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2021] [Accepted: 03/21/2021] [Indexed: 01/12/2023]
Affiliation(s)
- Chandra Veer Singh
- Department of Otorhinolaryngology, J.N. Medical College, Datta Meghe Institute of Medical Sciences, Sawangi Meghe, Wardha 442004, India.
| | - Shraddha Jain
- Department of Otorhinolaryngology, J.N. Medical College, Datta Meghe Institute of Medical Sciences, Sawangi Meghe, Wardha 442004, India
| | - Sana Parveen
- Department of Otorhinolaryngology, J.N. Medical College, Datta Meghe Institute of Medical Sciences, Sawangi Meghe, Wardha 442004, India
| | - Prasad Deshmukh
- Department of Otorhinolaryngology, J.N. Medical College, Datta Meghe Institute of Medical Sciences, Sawangi Meghe, Wardha 442004, India
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34
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Locatello LG, Trotta B, Bruno C, Trotta M, Maggiore G, Rasero L, Caini S, Gallo O. Systemic steroids may enhance recovery from loss of smell and taste in hospitalized coronavirus disease 2019 (COVID-19) patients: an observational study. Int Forum Allergy Rhinol 2021; 11:1689-1693. [PMID: 34132052 PMCID: PMC8427029 DOI: 10.1002/alr.22848] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Revised: 05/20/2021] [Accepted: 05/21/2021] [Indexed: 12/14/2022]
Affiliation(s)
| | - Benedetta Trotta
- Department of Otorhinolaryngology, Careggi University Hospital, Florence, Italy
| | - Chiara Bruno
- Department of Otorhinolaryngology, Careggi University Hospital, Florence, Italy
| | - Michele Trotta
- Department of Infectious and Tropical Diseases, Careggi University Hospital, Florence, Italy
| | | | - Laura Rasero
- Department of Health Sciences, University of Florence, Florence, Italy
| | - Saverio Caini
- Cancer Risk Factors and Lifestyle Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Florence, Italy
| | - Oreste Gallo
- Department of Otorhinolaryngology, Careggi University Hospital, Florence, Italy.,Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
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35
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Kasiri H, Rouhani N, Salehifar E, Ghazaeian M, Fallah S. Mometasone furoate nasal spray in the treatment of patients with COVID-19 olfactory dysfunction: A randomized, double blind clinical trial. Int Immunopharmacol 2021; 98:107871. [PMID: 34147912 PMCID: PMC8196319 DOI: 10.1016/j.intimp.2021.107871] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Revised: 06/07/2021] [Accepted: 06/08/2021] [Indexed: 01/06/2023]
Abstract
The aim of this study was to evaluate the usage of mometasone furoate nasal spray in the recovery of patients with severe microsmia or anosmia induced by COVID-19. This was a prospective clinical trial on non-hospitalized adult patients with COVID-19 (>18 years) who had severe microsmia or anosmia within two weeks. The subjects were randomly assigned to the mometasone furoate group (100 mcg twice daily) or sodium chloride group (0.9%); both groups also received olfactory training for 4 weeks. The primary outcome was the improvement of the olfactory score at the end of the study. Visual analog scale (VAS) and the University of Pennsylvania Smell Identification Test (UPSIT) were used to assess primary outcome. A total of 80 patients were recruited, 77 of them completed the study and were analyzed. There was no statistically significant difference in terms of demographics and baseline clinical characteristics. The olfactory scores (based on VAS) at weekly intervals showed a significant difference between the two groups (P:0.318, <0.001, <0.001, <0.001, respectively). The analyses also showed significant within-group differences from baseline. Nevertheless, the changes were not significant between the two groups (P: 0.444, 0.402, 0.267, 0.329). There was no significant difference between the two groups in terms of the UPSIT results (p > 0.239). However, a significant between-group difference was noted in the severity of loss of smell (P < 0.001). Compared to olfactory training, mometasone furoate nasal spray combination with olfactory training showed a higher improvement in severe chronic anosmia by COVID-19.
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Affiliation(s)
- Hossein Kasiri
- Department of Clinical Pharmacy, Faculty of pharmacy, Mazandaran University of Medical Sciences, Sari, Iran
| | - Nima Rouhani
- Department of Infectious Disease, Ibne Sina Medical and Educational Center, Mazandaran University of Medical Sciences, Sari, Iran
| | - Ebrahim Salehifar
- Pharmaceutical Research Center, Department of Clinical Pharmacy, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran
| | - Monireh Ghazaeian
- Pharmaceutical Research Center, Department of Clinical Pharmacy, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
| | - Sahar Fallah
- Department of Biostatistic, Ibne Sina Medical and Educational Center, Mazandaran University of Medical Sciences, Sari, Iran
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Neta FI, Fernandes ACL, Vale AJM, Pinheiro FI, Cobucci RN, Azevedo EPD, Guzen FP. Pathophysiology and possible treatments for olfactory-gustatory disorders in patients affected by COVID-19. CURRENT RESEARCH IN PHARMACOLOGY AND DRUG DISCOVERY 2021; 2:100035. [PMID: 34870148 PMCID: PMC8178068 DOI: 10.1016/j.crphar.2021.100035] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2021] [Revised: 05/14/2021] [Accepted: 05/18/2021] [Indexed: 12/13/2022] Open
Abstract
SARS-CoV-2 infects host cells mainly through the interaction between the virus's Spike protein and the viral receptors namely Angiotensin-Converting Enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). Both are highly expressed in the gastrointestinal tract, in the nasal and bronchial epithelium, as well as in the type II alveolar epithelial cells. The aim of this review is to report the evidences from the scientific literature on the pathophysiology and the available treatments for olfactory-gustatory disorders in patients with COVID-19. The mechanisms involved in these disorders are still unclear and studies on specific therapies are scarce. However, it has been hypothesized that a decrease in the sensitivity of the sensory neurons as well as the co-expression of ACE2 and TMPRSS2 in the alveolar epithelial cells are the main causes of olfactory-gustatory disorders. The possible mechanisms described in the literature for changes in taste perception in patients with COVID-19 include olfactory disorders and a competitive activity of COVID-19 on ACE2 receptors in the taste buds. In addition, SARS-CoV-2 can bind to sialic acid receptors in the taste buds. In general, evidences show that there is no specific treatment for olfactory-taste disorders induced by SARS-CoV-2, even though some treatments have been used and have shown some promising results, such as olfactory training, intranasal application of sodium citrate and vitamin A, as well as systemic use of omega-3 and zinc. Corticosteroids have also been used as a pharmacological approach to treat patients with olfactory dysfunction with some contradictory results. The knowledge of the mechanisms by which SARS-CoV-2 influences the sensory systems and how effective therapies can treat the loss of smell and taste will have important implications on the understanding and clinical management of olfactory-taste disorders.
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Affiliation(s)
- Francisca Idalina Neta
- Postgraduate Program in Physiological Sciences, Department of Biomedical Sciences, Faculty of Health Sciences, State University of Rio Grande do Norte (UERN), Brazil
| | - Amélia Carolina Lopes Fernandes
- Postgraduate Program in Physiological Sciences, Department of Biomedical Sciences, Faculty of Health Sciences, State University of Rio Grande do Norte (UERN), Brazil
- Nurse Department, Nurse School, State University of Rio Grande do Norte (UERN), Mossoró, Brazil
| | - Adson José Martins Vale
- Tocogynecology Department, Medical School, Federal University of Rio Grande do Norte (UFRN), Natal, Brazil
- Postgraduate Program in Biotechnology, Laureate International Universities – Potiguar University (UnP), Natal, Brazil
| | - Francisco Irochima Pinheiro
- Postgraduate Program in Biotechnology, Laureate International Universities – Potiguar University (UnP), Natal, Brazil
- Medical School, Laureate International Universities – Potiguar University (UnP), Natal, Brazil
| | - Ricardo Ney Cobucci
- Tocogynecology Department, Medical School, Federal University of Rio Grande do Norte (UFRN), Natal, Brazil
- Postgraduate Program in Biotechnology, Laureate International Universities – Potiguar University (UnP), Natal, Brazil
- Medical School, Laureate International Universities – Potiguar University (UnP), Natal, Brazil
| | - Eduardo Pereira de Azevedo
- Postgraduate Program in Biotechnology, Laureate International Universities – Potiguar University (UnP), Natal, Brazil
| | - Fausto Pierdoná Guzen
- Postgraduate Program in Physiological Sciences, Department of Biomedical Sciences, Faculty of Health Sciences, State University of Rio Grande do Norte (UERN), Brazil
- Postgraduate Program in Biotechnology, Laureate International Universities – Potiguar University (UnP), Natal, Brazil
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Langarizadeh MA, Ranjbar Tavakoli M, Abiri A, Ghasempour A, Rezaei M, Ameri A. A review on function and side effects of systemic corticosteroids used in high-grade COVID-19 to prevent cytokine storms. EXCLI JOURNAL 2021; 20:339-365. [PMID: 33746666 PMCID: PMC7975631 DOI: 10.17179/excli2020-3196] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Accepted: 02/09/2021] [Indexed: 12/13/2022]
Abstract
In December 2019, a cluster of pneumonia caused by a novel coronavirus (2019-nCoV), officially known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in Wuhan, Hubei province, China. Cytokine storm is an uncontrolled systemic inflammatory response resulting from the release of large amounts of pro-inflammatory cytokines and chemokines that occurs at phase 3 of viral infection. Such emergence led to the development of many clinical trials to discover efficient drugs and therapeutic protocols to fight with this single-stranded RNA virus. Corticosteroids suppress inflammation of the lungs during the cytokine storm, weaken immune responses, and inhibit the elimination of pathogen. For this reason, in COVID-19 corticosteroid therapy, systemic inhibition of inflammation is observed with a wide range of side effects. The present review discusses the effectiveness of the corticosteroid application in COVID-19 infection and the related side effects of these agents. In summary, a number of corticosteroids, including and especially methylprednisolone and dexamethasone, have demonstrated remarkable efficacy, particularly for COVID-19 patients who underwent mechanical ventilation.
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Affiliation(s)
- Mohammad Amin Langarizadeh
- Student Research Committee, Kerman University of Medical Sciences, Kerman, Iran
- Department of Medicinal Chemistry, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran
| | | | - Ardavan Abiri
- Student Research Committee, Kerman University of Medical Sciences, Kerman, Iran
- Department of Medicinal Chemistry, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran
| | - Ali Ghasempour
- Student Research Committee, Kerman University of Medical Sciences, Kerman, Iran
| | - Masoud Rezaei
- Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | - Alieh Ameri
- Department of Medicinal Chemistry, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran
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